This invention relates to a method of dispensing an opthalmic fluid from a portable container which includes a porous filter medium having bonded thereto an antimicrobial agent in order to eliminate contamination by microbial growth.
An antimicrobial is an agent that destroys or inhibits the growth of microorganisms. The major classes of microorganisms are bacteria, fungi including mold and mildew, yeasts, and algae. Microorganisms can be found in the air, the waters, the human body, soil, wastes, and on all surfaces. The organisms are deposited from the air, food and drink spills, dust, dirt and tracked in soil, and from human excreta such as sweat, urine, and feces. Organisms grow and multiply when there is available a nutrient source of food such as dirt, organic or inorganic material, and living tissue. For growth and multiplication, organisms also require warm temperatures, and moisture. When these conditions exist, microorganisms thrive and flourish. Microbial growth, however, leads to many problems such as unpleasant odors ranging from stale to musty and mildew-like, to putrid and foul smelling, resembling ammonia. The growths also produce unsightly stains, discoloration, and deterioration of many surfaces and materials in which they come into contact. A more serious disadvantage of microbial growth is the production of pathogenic microorganisms, germs, their metabolic products and their somatic and reproductive cell parts, which contribute to the spread of disease, infection, and disorders.
Antimicrobial agents are chemical compositions that are used to prevent such microbiological contaminations by inhibiting, killing and/or removing them and neutralizing their effects of deterioration, defacement, odor, disease or other negative effects. Particular areas of application of antimicrobial agents and compositions are, for example, cosmetics, disinfectants, sanitizers, wood preservation, food, animal feed, cooling water, metalworking fluids, hospital and medical uses, plastics and resins, petroleum, pulp and paper, textiles, latex, adhesives, leather and hides, and paint slurries. In the area of medical applications, antimicrobials are often used as powders, in lotions, creams, ointments and/or delivered in a variety of solvents or directly as over-the-counter or ethical drugs to alleviate, mediate, cure and/or protect people or other animals from disease or cosmetic conditions. Of the diverse categories of antimicrobial agents and compositions, quaternary ammonium compounds represent one of the largest of the classes of antimicrobial agents in use. At low concentrations, quaternary ammonium type antimicrobial agents are bacteriostatic, fungistatic, algistatic, sporostatic, and tuberculostatic. At medium concentrations they are bactericidal, fungicidal, algicidal, and viricidal against lipophilic viruses. Organosilicon quaternary ammonium salt compounds are well known as exemplified by U.S. Pat. No. 3,560,385, issued Feb. 2, 1971, and the use of such compounds as antimicrobial agents is taught, for example, in a wide variety of patents such as U.S. Pat. Nos. 3,730,701, issued May 1, 1973, and 3,817,739, issued June 18, 1974, where the compounds are used to inhibit algae; 3,794,736, issued Feb. 26, 1974, and 3,860,709, issued Jan. 14, 1975, where they are employed for sterilizing or disinfecting a variety of surfaces and instruments; and 3,865,728, issued Feb. 11, 1975, where the compounds are used to treat aquarium filters. PCT Application No. 8601457, published Jan. 15, 1987, teaches that microorganisms on multi-cellular plants and fruit can be killed by the application thereto of an aqueous mixture of a surfactant and an organosilicon quaternary ammonium compound. U.S. Pat. No. 4,564,456, issued Jan. 14, 1986, discloses organosilanes as anti-scale agents in water systems. In a particular application of an antimicrobial organosilicon quaternary ammonium compound, a paper substrate is rendered resistant to the growth of microorganisms in U.S. Pat. No. 4,282,366, issued Aug. 4, 1981. In U.S. Pat. No. 4,504,541, issued Mar. 12, 1985, an antimicrobial fabric is disclosed which is resistant to discoloration and yellowing by treatment of the fabric with a quaternary ammonium base containing an organosilicon compound. U.S. Pat. No. 4,781,974, issued Nov. 1, 1988, relates to wet wiper towelettes having an antimicrobial agent substantive to the fibers of the web and being an organosilicon quaternary ammonium compound. In U.S. Pat. No. 4,467,013, issued Aug. 21, 1984, such compounds are disclosed to be useful in surgical drapes, gowns, dressings, and bandages. Organosilicon quaternary ammonium compounds have been employed in carpets, in U.S. Pat. No. 4,371,577, issued Feb. 1, 1983; applied to walls, added to paints, and sprayed into shoes, in U.S. Pat. No. 4,394,378, issued July 19, 1983; applied to polyethylene surfaces and used in pillow ticking in U.S. Pat. No. 4,721,511, issued Jan. 26, 1988; in flexible polyurethane foams of fine-celled, soft, resilient articles of manufacture in U.S. Pat. No. 4,631,297, issued Dec. 23, 1986; and mixed with a surfactant in British Pat. No. 1,386,876, of Mar. 12, 1975. Some general, more domestic type applications of these compounds, has included their use in a dentifrice as in U.S. Pat. No. 4,161,518 issued July 17, 1979; in a novel laundry detergent in U.S. Pat. No. 4,557,854, issued Dec. 10, 1985; as a hair conditioner in U.S. Pat. No. 4,567,039, issued Jan. 28, 1986; and in a soft contact lens disinfectant solution in U.S. Pat. No. 4,615,882, issued Oct. 7, 1986. In U.S. Pat. No. 4,614,675, issued Sept. 30, 1986, properties can be influenced by mixing the organosilicon quaternary ammonium compounds with certain siloxanes.
Other typical uses of organosilicon quaternary ammonium compounds in accordance with the prior art can be seen from U.S. Pat. Nos. 4,005,028, issued on Jan. 25, 1977, and relating to hard surface rinse aids and detergents. Contact lenses are treated with an organosilane in U.S. Pat. No. 4,472,327, issued Sept. 18, 1984. In U.S. Pat. No. 4,682,992, issued July 28, 1987, glass spheres are treated with the compounds and employed as filters. The compounds are used to treat swine dysentery in U.S. Pat. No. 4,772,593, issued Sept. 20, 1988; applied to a polyester fabric in U.S. Pat. No. 4,822,667, issued Apr. 18, 1989; and adhered to a polyamide filament in U.S. Pat. No. 4,835,019, issued May 30, 1989. In Canadian Patent No. 1,217,004, granted Jan. 27, 1987, organosilane quaternary ammonium compounds are formulated into bleaches that are applied to hard surfaces such as bath tubs, wash basins, toilets, drains, and ceramic tile floors.
Among the numerous attempts to alleviate the problems of microorganisms on surfaces have involved the use of soaps, detergents, and surface cleaners. The treatments, however, have for the most part included an unbound category of antimicrobial which is not actually bonded to the surface sought to be treated, and therefore is consumed by the microorganisms, with the result that the unbound antimicrobial is depleted and washed away during routine cleansing. As this diffusion continues, the concentration of the active ingredient becomes diluted below effective levels, with the result that the microorganisms sought to be inhibited, adapt and build up a tolerance, becoming immune to what was once an effective treatment dose. Such unbound diffusible antimicrobials have therefore been found to be limited in their ability to offer broad spectrum control of microorganisms, in contrast to the bound type of antimicrobial which remains chemically attached to the surface to which it is applied providing for a surface that prevents recolonization by the microflora associated therewith. Diffusing types of antimicrobials also often suffer from the propensity to transfer percutaneously, giving rise to sensitization and irritation immunological responses, and raising serious questions as to their ultimate fate within the body and body systems.
The "unbound" antimicrobials of the prior art are not the equivalent of the "bound" antimicrobial organosilane of the present invention because the unbound antimicrobials do not perform substantially the same function, in substantially the same way, to produce substantially the same results, as do the bound silanes of the present invention. The function differs because the bound antimicrobial is permanent whereas the unbound types are easily washed away or rubbed from the surface. The compounds of the present invention are not only durable but retain their antimicrobial activity after some ten laundering cycles, and only slightly diminish in their activity after as many as twenty-five laundering cycles. The bound silanes of the present invention retain an effective kill level of microorganisms. The manner in which the bound silane functions differs from the unbound types, since the bound silane attaches itself to the surface to which it is applied, whereas the unbound types are mere coatings which are not substantive. This is significant since the silane antimicrobial will continue to prevent reinfestation, and enables one to utilize the intrinsic antimicrobial activity o the silane treated surface to kill transient microbes, long after the unbound types of antimicrobials have been depleted of their activity. Further, the bound silanes of the present invention destroy, reduce, and inhibit the growth and multiplication of bacteria, fungi, and other pathogenic microorganisms, by the disruption of cell membranes, a mechanism absent from conventional unbound antimicrobial materials. The results produced by the bound silanes is not the same as the results produced by the unbound types, since the bound silanes provide a prolonged antimicrobial activity and continue to kill and inhibit the proliferation of potentially destructive microorganisms, versus mere temporary and superficial protection offered by the unbound category of material. Thus, it should be apparent that the method of the present invention in employing the bound antimicrobially active organosilicon quaternary ammonium compounds is far removed from methods that have been previously disclosed by the prior art.
Bound antimicrobials kill organisms on contact and continue to kill organisms without being diffused or leached from the surface. Thus, the bound antimicrobial leaves behind an effective level of active ingredient and is able to control a broad spectrum of microorganisms including gram negative and gram positive bacteria, mold, mildew, fungi, yeast, and algae. An exemplary category of bound antimicrobial is an alkoxysilane quaternary ammonium compound, and such alkoxysilane quaternary ammonium compounds have been found to be more effective at reducing the number of microorganisms, and inhibiting microbially generated odors, than conventional organotin compounds and other organic quaternary ammonium compounds. The silanes of the present invention when delivered from simple water solutions immobilize on surfaces and bond thereto to provide a coating of immobilized antimicrobial, unlike conventional materials.
In the present invention, this bound characteristic of alkoxysilane quaternary ammonium compounds, as well as their capabilities of performing at effective kill levels beyond prior art types of compositions, is taken advantage of in the treatment of surfaces, in order to reduce or substantially eliminate the incidence of microorganisms, germs, their metabolic products and their somatic and reproductive cell parts, which contribute to the spread of such microbes.
It is not new to disinfect aqueous solutions in an attempt to rid the solutions of bacterial growth. For example, U.S. Pat. No. 1,204,171, issued Nov. 7, 1916, discloses a sanitary drinking tube which includes a body of disinfecting material. Water is said to be drawn through the disinfecting material and filtered or rendered free from contamination, although the exact nature and construction of the disinfecting material is not disclosed. In U.S. Pat. No. 4,483,771, issued Nov. 20, 1984, a liquid filter of multiple layers is taught, one layer of which is impregnated with an antibiotic bacteria destroying material such as penicillin, iodine, tetracycline, kanamycin, or sulfonamides. A dispenser for saline solution is taught in U.S. Pat. No. 4,463,880, issued Aug. 7, 1984. The saline dispenser includes a disinfectant soaked pad, although the composition of the disinfectant is not disclosed. In contrast, the present invention in one embodiment is directed specifically to opthalmic solutions and to the treatment of such solutions with a "bound" silane antimicrobial. Such a bound antimicrobial avoids the negative effects that traditional "unbound" antimicrobials possess. For example, it is known that many preservatives cause eye irritation to many people, and the foregoing unbound antimicrobials of the type noted immediately above in the '171, '771, and '880 patents would be no exception. In fact such unbound antimicrobials would in all likelihood possess irritation levels well in excess of the levels experienced with current preservative type compounds. This is particularly significant when it is considered that opthalmic solutions are traditionally administered in the form of drops directed to the area of the human eye. This highly sensitive area of the human anatomy is prone to irritation, and hence the presence of any leachable material in a filter medium used to treat such solutions which may tend to cause irritation to the eye should be avoided. Hence, the "bound" silane antimicrobial of the present invention offers significant advantages in that once the silane is chemically bonded to a surface such as a porous filter medium, the silane is substantive to that surface and is not carried away from the surface to the eye along with the filter effluent. In addition, the silane of the present invention maintains the ophthalmic solution in a sterile condition in the container, and causes any excess draining back into the container following administration to be re-sterilized. The addition of other preservatives for the ophthalmic solution is therefore eliminated.
The '171, '771, and '880 patents discussed above all suffer from the additional disadvantages in that the disinfectants and antibiotics disclosed therein are washable from the filter surfaces, and while some of the microorganisms may be killed to some extent, the solution sought to be preserved would actually become contaminated with the disinfectant or antibiotic. In leaching from the filter surfaces, the disinfectants would present the problem of raw toxicity to the eyes and skin, and a limited spectrum of activity. The antibiotics on the other hand, would create allergenic response sensitivities, a general chemical incompatability with the solution sought to be preserved, and the lack of a broad spectrum activity against a variety of microbial contaminates. Microorganisms also possess the capability of quickly adapting to most antibiotics.